4,6-Diaryl/heteroarylpyrimidin-2(1H)-ones as a new class of xanthine oxidase inhibitors

Shiwani Shukla, Dinesh Kumar, Ritu Ojha, Manish K. Gupta, Kunal Nepali, Preet M.S. Bedi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Summary A series of 4,6-diaryl/heteroarylpyrimidones was synthesized employing silica-supported fluoroboric acid under solvent-free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesized compounds were evaluated for in vitro xanthine oxidase (XO) inhibitory activity for the first time. Structure-activity relationship analyses are also presented. Among the synthesized compounds, VA-5, -9, -10, -12, -22, -23, and -25 were the active inhibitors with IC50 values ranging from 6.45 to 13.46 μM. Compound VA-25 with a pyridinyl ring as ring A and a thiophenyl ring as ring B emerged as the most potent XO inhibitor (IC50 = 6.45 μM) in comparison to allopurinol (IC50 = 12.24 μM). Some of the important interactions of VA-25 with the amino acid residues of the active site of XO were figured out by molecular modeling studies. A series of 4,6-diaryl/ heteroarylpyrimidones, synthesized by silica supported fluoroboric acid under solvent-free conditions in a microwave reactor, were evaluated for their in vitro xanthine oxidase inhibitory activities. VA-5, -9, -10, -12, -22, -23, and -25 were found to be active inhibitors with IC50 values ranging from 6.45 to 13.46 μM. Structure-activity relationship analyses are also presented.

Original languageEnglish
Pages (from-to)486-495
Number of pages10
JournalArchiv der Pharmazie
Volume347
Issue number7
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Fingerprint

Xanthine Oxidase
Inhibitory Concentration 50
Structure-Activity Relationship
Microwaves
Silicon Dioxide
Allopurinol
Catalytic Domain
Amino Acids
2,3-dihydro-6-(2,5-dimethoxyphenyl)imidazo(2,1-b)thiazole
In Vitro Techniques
fluoroboric acid

Keywords

  • Catalyst
  • Fluoroboric acid
  • Inhibitors
  • Microwave radiation
  • Pyrimidones
  • Silica
  • Xanthine oxidase

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery

Cite this

4,6-Diaryl/heteroarylpyrimidin-2(1H)-ones as a new class of xanthine oxidase inhibitors. / Shukla, Shiwani; Kumar, Dinesh; Ojha, Ritu; Gupta, Manish K.; Nepali, Kunal; Bedi, Preet M.S.

In: Archiv der Pharmazie, Vol. 347, No. 7, 01.01.2014, p. 486-495.

Research output: Contribution to journalArticle

Shukla, Shiwani ; Kumar, Dinesh ; Ojha, Ritu ; Gupta, Manish K. ; Nepali, Kunal ; Bedi, Preet M.S. / 4,6-Diaryl/heteroarylpyrimidin-2(1H)-ones as a new class of xanthine oxidase inhibitors. In: Archiv der Pharmazie. 2014 ; Vol. 347, No. 7. pp. 486-495.
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AB - Summary A series of 4,6-diaryl/heteroarylpyrimidones was synthesized employing silica-supported fluoroboric acid under solvent-free conditions in a microwave reactor. The catalytic influence of HBF4-SiO2 was investigated in detail to optimize the reaction conditions. The synthesized compounds were evaluated for in vitro xanthine oxidase (XO) inhibitory activity for the first time. Structure-activity relationship analyses are also presented. Among the synthesized compounds, VA-5, -9, -10, -12, -22, -23, and -25 were the active inhibitors with IC50 values ranging from 6.45 to 13.46 μM. Compound VA-25 with a pyridinyl ring as ring A and a thiophenyl ring as ring B emerged as the most potent XO inhibitor (IC50 = 6.45 μM) in comparison to allopurinol (IC50 = 12.24 μM). Some of the important interactions of VA-25 with the amino acid residues of the active site of XO were figured out by molecular modeling studies. A series of 4,6-diaryl/ heteroarylpyrimidones, synthesized by silica supported fluoroboric acid under solvent-free conditions in a microwave reactor, were evaluated for their in vitro xanthine oxidase inhibitory activities. VA-5, -9, -10, -12, -22, -23, and -25 were found to be active inhibitors with IC50 values ranging from 6.45 to 13.46 μM. Structure-activity relationship analyses are also presented.

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